The present invention is directed to an apparatus and method of its use for determining non-invasively the concentrations of certain blood analytes. More particularly, the invention is directed to a low cost apparatus intended for home use by diabetics to monitor and measure blood glucose levels.
Persons suffering from diabetes may typically monitor their own glucose concentrations with periodic daily measurements, usually four times each day. Present methods require the diabetic to draw a blood sample for each test and to use a chemical reagent in the test procedure for measuring glucose concentration. Blood extractions for such tests often become a real burden to the diabetic and, in addition, the chemical reagents used in the tests are quite expensive, particularly in view of the large number of tests required. Therefore, a simple and accurate method and apparatus for non-invasively measuring glucose concentration would be most desirable. Further, such an apparatus which could be supplied at relatively low cost and used by a diabetic at home, in place of present invasive techniques, is particularly desirable.
Various kinds of apparatus and related methods for the non-invasive determination of glucose concentrations, as well as concentrations of other blood analytes, are known in the art. European Pat. Application No. 84840212, filed May 4, 1984 (Publication No. 0160768, dated Nov. 13, 1985) describes such an apparatus and its method of use. The described method uses dispersive technology in which a monochromator directs two or more separate wave lengths of light into body tissue, either transmissively or reflectively, for individual glucose absorbance measurements. A microprocessor then calculates the glucose concentration from the series of such absorbance measurements. The techniques and apparatus described in the above identified application are typical of the traditional methods of near infrared analysis based on the measurement of absorbance at a single or multiple specific wavelengths.
Non-invasive, in vivo monitoring of oxidative metabolism, utilizing both transmissive and diffuse reflective methods, is disclosed in U.S. Pat. Nos. 4,281,645 and 4,223,680, respectively. However, both patents describe techniques utilizing the measurement of infrared light absorbance at specific individual wavelengths.
The concentrations of certain major blood compounds, such as glucose and cholesterol, are much lower than concentrations of compounds typically analyzed by near infrared spectrometry. Glucose concentration averages only about 0.1% by weight (1000 ppm) of blood serum. Furthermore, an accuracy of.+-.50 ppm is required for any meaningful measurement of concentration. Thus, sensitivity to IR absorption measurements has traditionally been a problem in determining glucose concentration. Another problem concerns the existence of other blood serum components which compete with glucose as light absorbers in the near infrared spectral region where glucose is moderately or strongly absorbing. Thus, interference from such competing components as proteins and water has typically been a problem. In addition, the concentrations of serum proteins are significantly higher than glucose in the spectral regions of interest, thereby compounding the interference problem.
It is also recognized that there are practical limits on the spectral bandwidth in the near infrared region which can be used for meaningful glucose measurements and that reflective and transmissive measurements cannot both be used effectively over that bandwidth. At wavelengths less than about 900 to 1,000 nm (nanometers), other strongly absorbent materials also exist and the specific absorption due to glucose may be too small to provide the necessary sensitivity and accuracy, particularly in view of the interfering absorbers. In the range of 1000 to 1800 nm, glucose absorption is somewhat improved, but still relatively low. IR absorbence by glucose in the range of 1800 to 2800 nm is much greater and, at least theoretically, higher absorbance in this range should provide sufficient sensitivity to accurately measure glucose concentrations. However, at wavelengths greater than 1800 nm, light is strongly absorbed by water and has little penetration capability into glucose-containing tissue, despite the high specific absorption by glucose at these wavelengths. As a result, transmissive measurements in the region above about 1800 nm are impractical.
Non-dispersive correlation spectrometry, utilizing a relatively wide infrared spectral band, has long been used in gas analysis, such as engine gas emission analysis. A gas-filter correlation spectrometer correlates spectral absorption signals from the gas being measured and a gas in a filter. In particular, systems utilizing a so-called "negative filter" have been found to be particularly effective and exhibit a low sensitivity to interfering gases. One such system is described in Cha and Gabele, "Study on Infrared Gas-Filter Correlation Spectrometer for Measuring Low-Concentration Methanol Gases", Optical Engineering, Volume 25, No. 12, pages 1299-1303 (December 1986). However, gas filters used in gas correlation cells are relatively easy to make and use. A gas correlation cell typically comprises a sealed glass or plastic cell that contains the gas of interest at a predetermined concentration. A liquid correlation cell, on the other hand, is much more difficult to design, make and use and, to applicant's knowledge, the principles of gas filter correlation spectrometry have not been applied to liquid analysis.
There is a particular need today for a non-invasive instrument which could be used by the diabetic at home for measuring and monitoring glucose levels. Such a device would eliminate the need for chemical tests requiring expensive reagents, as well as the burden and trauma associated with multiple daily blood sampling. The device should also be relatively low in cost and, ideally, be less than the annual cost of current invasive methods.